This R01 application responds to NIDA PA08-127 Prescription Drug Misuse by investigating the mechanisms linking non-medical prescription drug use (NMPD) with injection drug use (IDU). A central focus is also how these relations differ by HIV status and HIV risk behaviors. Most studies of NMPD have either recruited samples that do not include IDUs or have not examined them as a distinct group. This lack of attention to the unique needs of IDUs may hamper the progress of clinical and public health efforts to prevent, identify, and treat NMPD, and to effectively address HIV risk behaviors and wellness among IDUs. A critical barrier to designing and implementing interventions for NMPD is that the term nonmedical use captures a heterogeneous range of motivations for use. These motivations for NMPD may be broadly categorized as euphoric (e.g., combining illicit and prescription drugs for greater effect) and self-treatment (e.g., use without a legitimate prescription to alleviate physical pain, negative mood, or drug withdrawal). Further, there may be important differences in the sources (e.g., health clinics, Emergency Department [ED], pharmacy, friends) and mechanisms (e.g., theft, sharing) used in procuring prescription medications based on underlying motivations for use. Prior work typically has combined multiple motivations into a single category of NMPD. Therefore, innovative studies, such as those targeting high volume consumers like IDUs, are needed to disaggregate NMPD into subtypes based on motivations for use. Information on NMPD motivational subtypes and associated characteristics (e.g., sequences of onset, patterns and predictors of consumption and acquisition) is an important area for future research, as those using for self-treatment may require different intervention strategies from those who use for euphoria. Using targeted sampling, we will recruit 750 IDUs in San Francisco and collect life history data at a baseline assessment and conduct a 6-month follow-up to: Aim 1: Assess the lifetime patterns of initiation and current consumption practices for IDU and NMPD, and differences in relation to HIV status and HIV risk behaviors; Aim 2: Examine the influence of biological, psychological, and social-contextual characteristics on NMPD and motivational subtypes of NMPD; Aim 3: Characterize the sources, mechanisms, and perceived access to NMPD, and examine differences by motivational subtypes of NMPD; Aim 4: Characterize how access to health care (e.g., substance abuse treatment, HIV care) influences consumption patterns and diversion practices.